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BIOFEST INVEST APPLICANT
RiverWalk Therapeutics, Inc.
- 8511 Mantano Ridge, Helotes, Texas 78023, US
- www.riverwalktherapeutics.com
Company Contact:
Legal Entity Type: C-Corp
Company Type: Pharmaceutical
Company Stage: Development
No. of Employees: 2
Desired Financial Amount: $2,500,000
Background
Company Background
RiverWalk is an entirely women-owned early-stage drug development company founded in 2019 as a Texas corporation based in San Antonio, TX. RiverWalk Therapeutics was spun out from UT Health San Antonio in 2019 to commercialize several novel small molecule inhibitors of adenosine signaling developed in the UTHSA lab of our founder, Dr. Jean Jiang. Dr. Jiang’s focus in recent years has been breast cancer metastasis in the bone, specifically the role of ATP and ATP byproducts in the progression of breast cancer metastasis. Through this work, Dr. Jiang’s lab was one of the first to identify the role and mechanisms of action of adenosine (a degradation product of ATP) in promoting metastasis and suppressing the immune response in the tumor microenvironment. She developed a suite of novel, patented small molecules that bind strongly to adenosine A2 receptors (A2A and A2B) with the hopes of making a significant difference in the disease progression. This work has led to the identification of several compounds that have significant, proven effects in metastatic triple negative breast cancer and preliminary in vitro results in several other cancers as well.
After company formation, she recruited Ms. Johanna Webb, to lead the company as President. She had worked with previously with Ms. Webb with great success at a previous start-up where they worked together to advance two assets through preclinical studies, regulatory submission, and into clinical trials. Together, they are continuing the development on these very promising molecules. RiverWalk has continued to attract support from the cancer drug development community with their selection as a participant in the 2022 TMCinnovation CPRIT-funded Accelerator for Cancer Therapeutics and the 2022 AIM-HI Women’s Venture Competition First Place Winner with Distinction.
Management
The RiverWalk team brings a synergistic combination of expertise in cancer research and early drug development that will facilitate the development of these molecules. Dr. Jiang and Ms. Webb have a joint history of successful drug development in two programs that both advanced to clinical trials. They have an established productive collaboration and a complementary set of skills and expertise when working together. Additionally, RiverWalk has a highly-experienced team of drug development consultants and advisors with deep expertise in small molecules to assist in the development process.
Johanna Webb, President, is an experienced Drug Development Project Manager with a demonstrated history of working in the biotechnology industry. Johanna is skilled in project management (30+ years), technology evaluation, pre-clinical development, rare pediatric and orphan diseases, and regulatory submission preparation. She holds a Master of Science (MS) in Biotechnology from The University of Texas at San Antonio and Bachelor of Science degrees in Biochemistry and Chemical Engineering from Texas A&M University. Ms. Webb was previously a Engineering Project Manager for McDonnell Douglas on the space station environmental systems, the President of Aspen Consulting Group, and a Commercialization Assessment Consultant for UT Health San Antonio. Immediately before joining the RiverWalk team, she was the Associate Director of Drug Development Project Management for AlaMab Therapeutics, a clinical-stage start-up biotech company. There she was responsible for the completion of pre-IND and IND documents on two different projects, the completion of Orphan Drug and Rare Pediatric Disease Designation filings, all of which were successfully awarded by the FDA, and acted as the leader of multi-disciplined teams of consultants, clinicians, and CROs to develop and implement clinical development plans and the resulting regulatory filings.
Dr. Jean Jiang, Founder & CSO, is the Zachry Distinguished University Professor in Cancer Research at UT Health San Antonio with 25+ years in cancer research. Dr. Jiang previously co-founded AlaMab Therapeutics, where she worked with Ms. Webb. AlaMab advanced 2 assets into clinical trials due in large part to Dr. Jiang’s contributions and Ms. Webb’s leadership. Dr. Jiang received her Ph.D. from the State University of New York at Stony Brook and did her postdoctoral training at Harvard Medical School. She was a research faculty there before she joined UT Health San Antonio as a faculty member. She has authored 170+ peer-reviewed publications with over 20,000 citations. Her research primarily focuses on connexin hemichannels in bone and cancer bone metastasis. Her lab has developed both cell-based and in vivo animal models. Her research has been continuously funded by grants from the NIH, DoD, and other funding agencies. She is a Fellow of the American Association for Advancement of Science (AAAS) and National Academy of Inventors (NAI), and the recipient of the Cancer Therapeutic Research Center Discovery of the Year Award, Master Research Award for Distinguished Researcher, and Presidential Distinguished Senior Research Award. She has served as an associate and an editorial board member for multiple journals including eLife, the Journal of Biological Chemistry, Matrix Biology, and BMC Cell Biology, as well as a member of many US and international research review and advisory panels.
Board of directors
The RiverWalk Board of Directors currently consists of Dr. Jiang (chairman of the board) and Ms. Webb (President and acting CEO). RiverWalk is currently raising a seed round, and the lead investor will likely take a board position. Additionally, we are actively seeking an experienced and well-connected independent board member to help advise the company through these critical, formative years. Future funding rounds are expected to require additional board seats for the lead investor of each round.
Product / Service
disease area / application
Metastatic Cancers – particularly triple negative breast cancer, kidney cancer, ovarian cancer, and non-small cell lung cancer
product / Service
10-15% of the 280k breast cancers diagnosed annually are TNBC, which has high recurrence rates and mortality, often affects younger patients (<40 years old), and disproportionately affects Black and Hispanic women. TNBC is aggressive, spreads quickly, and is more likely to recur, with the highest rate of recurrence within 5 years. Today, 45% of TNBC patients advance to Stage 4, even after treatment, and their 5-year survival rate drops from ~90% to 50%). RW-108 is easily manufactured (>97% purity), has low toxicity, has acceptable “druggable” characteristics, and is orally bioavailable.
technology / ip
Our technology is a suite of novel small molecule compounds that inhibit certain adenosine-mediated signaling pathways with high affinity, specificity and efficacy. Below are the composition of matter patents that have been submitted and their issue status. Additionally, RiverWalk Therapeutics has an option for the exclusive, worldwide license from University of Texas Board of Regents, the sole assignee.
PENDING PATENT APPLICATION(S):
Hong Kong, Filed 4/20/2018, App. No. 18105200.5, Status: Pending
Canada, Filed: 8/17/2017, App. No. CA2,977,044, Status: Pending
Hong Kong, Filed: 1/16/2018, App. No. 18100597.7, Status: Pending
Europe, Filed: 7/18/2017, App. No. EP16737981.7, Status: Pending
ISSUED PATENT(S):
United States, Filed: 7/17/2017, Patent No. 10,214,529, Status: Issued 2/26/2019
China, Filed: 9/17/2017, Patent No. CN107428753, Status: Issued 3/3/2020
PATENT FAMILY:
https://patents.google.com/patent/WO2016115487A1/en?oq=WO2016115487
distribution channels
RiverWalk’s business model centers around developing our assets to major value inflection points that increase the product value and de-risk the technology in parallel. This will increase interest from a potential strategic partner/acquirer, likely a large- or mid-sized pharma company. Antagonism of A2 receptors has gained more attention in recent years and many larger pharma oncology companies are looking to add A2R antagonist assets to their portfolios, particularly those with strong oncology portfolios and synergistic therapeutics. Multiple large pharma organizations have expressed interest in this pathway to RiverWalk pending positive Phase 1 data.
Distribution of our drug after FDA approval will be impacted by the success of the insurance reimbursement strategy and the buy-in of breast oncology key opinion leaders to prescribe the therapy. RiverWalk is fostering support in the oncology community at every opportunity. The development of these molecules has been supported by the MD Anderson/Mays Cancer Center 2022 Drug Development Pilot grant and this continuing relationship will be important when competing for clinical trial and patient enrollment priority in the crowded TNBC space. Our advisor, Dr. Virginia Kaklamani, is a KOL in breast cancer oncology and will be critical to heighten awareness of RiverWalk’s development program. Also, technical publications, presentations, and collaborations are core tenets of our G2M strategy.
No later than the initiation of Phase 2 clinical trials, RiverWalk will require a partner(s) that has deep expertise in large-scale manufacturing, regulatory, reimbursement, and marketing to complete the clinical trial process and transition the product to market successfully through their pre-existing channels. RiverWalk is open to all forms of collaboration/exit for the benefit of the development, including out-licensing of the technology, a strategic partnership, or M&A.
market size
The global market for breast cancer therapeutics is competitive and growing, registering $25.5B in 2022 and is estimated to experience an 8% CAGR from 2022 through 2028. However, the global TNBC-specific drug market was $1.3B in 2022 and is expected to reach $2.7B by 2028 at a CAGR of 13%. Geographically, the market is dominated equally by two regions, the US and China, with a significant contribution from the EU. Specifically for late-stage TNBC patients, there are approximately 100k late-stage TNBC patients actively managing their TNBC each year in US, China, and EU at an average cost of $200k/patient/year, leading to a total treatment cost (drugs, radiation, surgery, etc.) of $20B annually in those markets.
RiverWalk is focused on improving the lives of TNBC patients, however, A2BR involvement is indicated in several other cancers. The RW-108 mechanism of action is dual, having a direct effect on both tumor cells (A2BR) and immune cells (A2BR and A2AR); and A2BR overexpression is correlated with a poorer prognosis in many cancers (Figs. 1 & 2). Therefore, tumors that are immunogenic and overexpress A2BR are expected to be the most responsive to RW-108 (Fig. 10). These cancers include kidney, esophageal, ovarian, stomach, head and neck, and non-small cell lung cancer (NSCLC).
Beyond oncology, A2BR is upregulated in many tissues in response to ischemia, inflammation, and injury. For example, A2BR stimulates water secretion in the digestive tract and modulates inflammatory responses and lower-GI motility, which have been indicated as a pathological mechanism of action in irritable bowel disease (IBS), secretory diarrhea, and inflammatory bowel disease. Adenosine signaling has also been implicated as a key player in the inflammatory and fibrotic response in renal fibrosis and idiopathic pulmonary fibrosis (IPF).
competition
Standard of Care
Treatment options are limited for most late-stage TNBC patients and almost 50% of TNBC patients still advance to Stage 4, reducing their 5-year survival to less than 15%. Because TNBC is HR-/HER2-, popular and widely-used HR- and HER2-directed therapies are not effective. Also, most TNBC patients do not have identified markers (BRCA, PD-L1) limiting use of these targeted therapies as well. Thus, management of metastatic TNBC usually consists of rounds of treatment using different chemotherapies until all options are exhausted. RW-108’s unique and multifaceted MOAs will overcome the barriers of conventional therapies, including toxicity and drug resistance. Because of its strong efficacy, RW-108 could potentially be used as a monotherapy or may provide a superior efficacy in combination with these treatments, rather than compete against them.
A2BR Antagonists
The few approved A2R antagonists are non-specific for all four subtypes of adenosine receptors (caffeine, theophylline). There are 3 other development programs developing dual AR antagonists: Arcus, Incyte, and Merck.
• Preclinical mouse data comparisons with other molecules in development highlight the superior characteristics of RW-108: target potency, mouse primary tumor reduction, and/or dosing regimens.
• The approach to primarily target A2BR, with its tumor-directed effects and multiple MOAs, and secondarily target A2AR, with its additional effects on the local immune system, is only found in RiverWalk’s molecules. RW-108 has very strong, single-digit nM potency for A2BR but is 4x less potent in inhibiting A2AR. In comparison with the other 3 bi-specific molecules, AB928 is equally potent for both receptors (single digit nM) and both INCB106385 and M1069 inhibit A2AR more potently than A2BR, ~40X and ~70X, respectively. The potential for off-target effects is expected to increase as the potency for A2AR increases.
• AB928 (Etrumadenant) is the most advanced program, having recently entered Phase 2 clinical trials only as a combination therapy. A direct comparison of preclinical mouse data for RW-108 and AB928 shows that RW-108 results in 3x the primary tumor reduction using 5% of the drug concentration. Also, head-to-head in vitro metastasis studies show that RW-108 inhibits tumor cell migration by more than 80% at ½ the IC50, as compared to 50% inhibition by AB928.
Financials
Desired financial amount
$2,500,000
previous funding
Nondilutive funding:
$110,000
Dr. Jiang’s discretionary endowment funds for the efficacy studies performed to date
MD Anderson/Mays Cancer Center Drug Development Pilot Award – $100k
AIM-HI Women’s Venture Competition 2022 First Place Winner with Distinction – $10k prize
Dilutive Funding:
$100,000
RiverWalk is raising a $2.5MM seed round. Cephalo Ventures has committed $100k, pending lead investor identification. Also, Krea Medica is interested in joining the seed round ($50k-75k) ,as well as providing preclinical and clinical support.
current financials
To date, continuing research and development has been funded within Dr. Jiang’s lab using discretionary endowment funds and the 2022 MD Anderson/Mays Cancer Center Drug Development Pilot Award. Project management, fund raising, and operational business activities are being performed by Ms. Webb and Dr. Jiang without salary at this time. Scientific and business expertise assistance is being provided mostly pro bono by resources provided through the TMCinnovation accelerator or other mentors. Other expenses are minimal and are being funded when necessary with award funds from the AIM-HI Women’s Venture Competition ($10k). All of this combines to result in minimal accrued debt thus far and a burn rate that is negligible.
financial use
The current seed round of $2.5 million would fund development efforts for the next 12-18 months including the remaining efficacy studies (MTD, dose dependent efficacy, PDX model validation), remaining drug characterization studies (safety panels, metabolite assessments, continuing PK studies), formulation studies for animal administration in IND-enabling studies, and manufacturing process analysis and scale-up engineering, as well as corporate operational expenses. A follow-on Series A round of approximately $13 million will be required for GLP/GMP manufacturing, IND-enabling toxicology and safety studies in rats and dogs, regulatory documentation preparation and submittal, and completion of Phase 1 studies.
revenue
With the long time horizon of drug development and the most common exit being an acquisition prior to completing clinical trials, RiverWalk will likely not generate revenue during its operational lifetime, with returns to investors being realized from the increased value of the de-risked assets upon the sale of the company. Funding during this time will be provided by non-dilutive grants (DoD, NIH, CPRIT, etc.) and equity investment. Additional funding could also come from a strategic partnership or limited out-licensing which would result in milestone payments to help fund the continued development of the assets.
exit strategy
RiverWalk’s expertise is targeted toward early drug development activities. The current development plan is to progress our drug candidate through preclinical development, regulatory submittal and approval, and into early clinical trials. Funding for these activities is being actively sought through government and other non-profit development grants (e.g. NIH STTR. DoD, CPRIT), equity investors, and/or industry partnerships.
RiverWalk will require a larger pharmaceutical organization that has deep expertise in large-scale manufacturing, regulatory, reimbursement, and marketing to complete the clinical trial process, gain approval, and transition to market. This occurs most often after completion of Phase 1 or the receipt of positive early data from Phase 2. An industry partnership at an earlier stage would significantly increase the speed of the development process. RiverWalk would consider an out-licensing of the technology, a strategic partnership, or an outright acquisition to accomplish the later-stage objectives.
